Robots Never Rest

Kip Guy, PhD (at left), Chemical Biology and Therapeutics chair, confers with Richard Gilbertson, MD, PhD, director of the St. Jude Comprehensive Cancer Center. The instrument behind them is a state-of-the-art robot, capable of testing tens of thousands of chemicals in a single day for the ability to destroy childhood cancer cells.

It is past noon in the Department of Chemical Biology and Therapeutics (CBT) at St. Jude Children’s Research Hospital. Some scientists are bent over experiments, hoping to snatch a quick bite to eat later. Others are down the hall in the lunchroom, taking a much-needed break with their colleagues.

But Billy the Robot is still working. All day long, his arms swing silently back and forth with a single purpose: to discover drugs that can help save kids’ lives.

In a single day, Billy can test tens of thousands of chemicals, seeking a small handful with the ability to kill cancer cells while sparing normal cells. The cancer cells come from some of the most aggressive and hard-to-treat childhood tumors. The chemicals come from, well, everywhere.

“Creating new drugs for pediatric cancers requires discovery on an industrial scale,” says Richard Gilbertson, MD, PhD, director of the St. Jude Comprehensive Cancer Center. “We have chemicals from all over the planet—the bottom of the ocean, the Amazon jungle—and they cover every chemical space you can imagine.”

The St. Jude collection contains more than 800,000 unique, purified molecules and is one of the largest chemical libraries at any academic institution in the world. Thousands of these chemicals have been isolated from natural sources. Others are existing drugs, already used to treat different diseases. More than 50,000 are new molecules, created in-house by St. Jude chemists.

It is no surprise that Billy and his robot colleagues, under the expert direction of Taosheng Chen, PhD, are prized on campus for their ability to rapidly test so many chemicals with outstanding fidelity. (The robots were named by St. Jude patients; others are Saver, Tobor and Clifford.)

The robot-based testing approach, called high-throughput screening, has proven a powerful way to find existing drugs with potential new uses against childhood cancers. It is one of many methods used at St. Jude to identify promising new agents that have never been tested in patients.

However, for truly driving drug discovery, humans still rule. “People see the robots, and they think they’re pretty snazzy,” observes Kip Guy, PhD, who spearheads the St. Jude drug discovery effort as chair of CBT. “But the robots are just one part of a workflow.”

Once a new molecule is identified, it is usually still years away from becoming a drug. Careful refinements must be made and tested to create a safe and effective drug for patients. This process requires untold hours of meticulous lab work and lively discussion among teams of scientists.

“To make a drug, everything has to come together in exactly the right way,” Guy says. “It’s the people, the science, the materials and the equipment; you need all of those things working together in order to be successful.”